3RPN

Crystal structure of human kappa class glutathione transferase in complex with S-hexylglutathione

Summary for 3RPN

• Entry DOI: 10.2210/pdb3rpn/pdb
• Related: 3RPP
• Descriptor: Glutathione S-transferase kappa 1, S-HEXYLGLUTATHIONE (3 entities in total)
• Functional Keywords: kappa gst, trx domain, gsh binding, detoxification, gtx, glutathione transferase inhibitor complex, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Peroxisome : Q9Y2Q3
• Total number of polymer chains: 6
• Total formula weight: 161955.04

Authors

Wang, B.,Peng, Y.,Zhang, T.,Ding, J. (deposition date: 2011-04-27, release date: 2011-07-13, Last modification date: 2023-11-01)

Primary citation

Wang, B.,Peng, Y.,Zhang, T.,Ding, J.
Crystal structures and kinetic studies of human Kappa class glutathione transferase provide insights into the catalytic mechanism.
Biochem.J., 439:215-225, 2011

PubMed Abstract: GSTs (glutathione transferases) are a family of enzymes that primarily catalyse nucleophilic addition of the thiol of GSH (reduced glutathione) to a variety of hydrophobic electrophiles in the cellular detoxification of cytotoxic and genotoxic compounds. GSTks (Kappa class GSTs) are a distinct class because of their unique cellular localization, function and structure. In the present paper we report the crystal structures of hGSTk (human GSTk) in apo-form and in complex with GTX (S-hexylglutathione) and steady-state kinetic studies, revealing insights into the catalytic mechanism of hGSTk and other GSTks. Substrate binding induces a conformational change of the active site from an 'open' conformation in the apo-form to a 'closed' conformation in the GTX-bound complex, facilitating formations of the G site (GSH-binding site) and the H site (hydrophobic substrate-binding site). The conserved Ser(16) at the G site functions as the catalytic residue in the deprotonation of the thiol group and the conserved Asp(69), Ser(200), Asp(201) and Arg(202) form a network of interactions with γ-glutamyl carboxylate to stabilize the thiolate anion. The H site is a large hydrophobic pocket with conformational flexibility to allow the binding of different hydrophobic substrates. The kinetic mechanism of hGSTk conforms to a rapid equilibrium random sequential Bi Bi model.

PubMed: 21728995
DOI: 10.1042/BJ20110753

Experimental method

X-RAY DIFFRACTION (1.9 Å)